Investigating the health status of primary school children in Tonga: Lessons learnt and reflections on field work in the Pacific Islands.

Globally, the child health focus has been on reducing under-5-year mortality, with large populations in low-resource regions prioritised. Children in older age groups, particularly in less populated regions such as the Pacific, have received limited attention. Child health research in the Pacific region has been lacking, and research approaches for the region have historically been from Western biomedical paradigms. We completed the study of primary school children's health over a period of 5 years. Firstly, we conducted a literature review, then we completed an audit of hospital admissions of primary school children, then we completed a two-round Delphi process and finally, we piloted the survey in three primary schools. Our results found there were high levels of oral health problems, ear health, obesity and exposure to violence and poverty impacting on the quality of health of primary school-age children. Identifying these indicators was made possible by the partnerships and trust established by the study team and provides specific and measurable targets for future work to improve the quality of child health outcomes. This paper describes key field work lessons learnt for research in the Pacific region. It must: (i) be on the platform of relationship, cultural safety and local ownership; (ii) include consideration of holistic Pacific paradigms of health; (iii) be adaptive to the context and environment; and (iv) be committed to long-term partnership and work.

Prevalence and maternal determinants of early and late introduction of complementary foods: results from the Growing Up in New Zealand cohort study.

A nationally generalisable cohort (n 5770) was used to determine the prevalence of non-timely (early/late) introduction of complementary food and core food groups and associations with maternal sociodemographic and health behaviours in New Zealand (NZ). Variables describing maternal characteristics and infant food introduction were sourced, respectively, from interviews completed antenatally and during late infancy. The NZ Infant Feeding Guidelines were used to define early (≤ 4 months) and late (≥ 7 months) introduction. Associations were examined using multivariable multinomial regression, presented as adjusted relative risk ratios and 95 % confidence intervals (RRR; 95% CI). Complementary food introduction was early for 40·2 % and late for 3·2 %. The prevalence of early food group introduction were fruit/vegetables (23·8 %), breads/cereals (36·3 %), iron-rich foods (34·1 %) and of late were meat/meat alternatives (45·9 %), dairy products (46·2 %) and fruits/vegetables (9·9 %). Compared with infants with timely food introduction, risk of early food introduction was increased for infants: breastfed < 6months (2·52; 2·19-2·90), whose mothers were < 30 years old (1·69; 1·46-1·94), had a diploma/trade certificate v. tertiary education (1·39; 1·1-1·70), of Maori v. European ethnicity (1·40; 1·12-1·75) or smoked during pregnancy (1·88; 1·44-2·46). Risk of late food introduction decreased for infants breastfed < 6 months (0·47; 0.27-0·80) and increased for infants whose mothers had secondary v. tertiary education (2·04; 1·16-3·60) were of Asian v. European ethnicity (2·22; 1·35, 3·63) or did not attend childbirth preparation classes (2·23; 1·24-4·01). Non-timely food introduction, specifically early food introduction, is prevalent in NZ. Interventions to improve food introduction timeliness should be ethnic-specific and support longer breast-feeding.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING: None.

Vitamin D status at birth and acute respiratory infection hospitalisation during infancy.

BACKGROUND: Hospital admission for acute respiratory infections (ARIs) during early childhood is a global public health concern. Vitamin D deficiency is prevalent during pregnancy and infancy. Evidence indicates that vitamin D supplementation prevents ARIs. OBJECTIVES: To determine whether vitamin D deficiency at birth is associated with ARI hospitalisations during infancy. METHODS: We performed a nested case-control study in children aged 0-12 months. Cases had ≥1 ARI hospitalisation and 4 controls were individually matched to each case. Newborn 25(OH)D concentration was measured on dried blood spots using two-dimensional liquid chromatography-tandem mass spectrometry. Hospital admissions were measured using health care records. Median serum 25(OH)D concentration in cases and controls was compared, and covariates of ARI hospitalisation during infancy were assessed using conditional logistic regression analysis. RESULTS: Six per cent of the cohort (n = 384) had an ARI hospitalisation during infancy, and 1536 controls were matched to cases. Median DBS [25(OH)D] was lower among ARI cases than controls (46 nmol/l vs. 61 nmol/L). Median 25(OH)D levels were lower for those hospitalised ≥2 times (47, IQR 36, 58) vs. those hospitalised once (52, IQR 42, 62) vs. the controls and also lower for those who stayed in the hospital for ≥3 days (45, IQR 36, 54) vs 1-2 days (48, IQR 38, 59) compared to the controls. After adjustment for season of birth and covariates describing demographic, antenatal, perinatal, and infant characteristics, DBS 25(OH)D concentration (<50 nmol/L) at birth was associated with increased odds of ARI hospitalisation during infancy (odds ratio 2.20, 95% confidence interval 1.48, 2.91). CONCLUSIONS: Vitamin D deficiency at birth is associated with increased odds of ARI hospitalisations in infants. The findings have implications for a developed country like New Zealand where vitamin D supplementation is not routinely recommended and the burden of ARI hospitalisation in young children is high.

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed. METHODS: Systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633). FINDINGS: We identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger's test). INTERPRETATION: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation. FUNDING: None.

A comparison of the effect of a Growing Up Milk - Lite (GUMLi) v. cows' milk on longitudinal dietary patterns and nutrient intakes in children aged 12-23 months: the GUMLi randomised controlled trial.

The second year of life is a period of nutritional vulnerability. We aimed to investigate the dietary patterns and nutrient intakes from 1 to 2 years of age during the 12-month follow-up period of the Growing Up Milk - Lite (GUMLi) trial. The GUMLi trial was a multi-centre, double-blinded, randomised controlled trial of 160 healthy 1-year-old children in Auckland, New Zealand and Brisbane, Australia. Dietary intakes were collected at baseline, 3, 6, 9 and 12 months post-randomisation, using a validated FFQ. Dietary patterns were identified using principal component analysis of the frequency of food item consumption per d. The effect of the intervention on dietary patterns and intake of eleven nutrients over the duration of the trial were investigated using random effects mixed models. A total of three dietary patterns were identified at baseline: 'junk/snack foods', 'healthy/guideline foods' and 'breast milk/formula'. A significant group difference was observed in 'breast milk/formula' dietary pattern z scores at 12 months post-randomisation, where those in the GUMLi group loaded more positively on this pattern, suggesting more frequent consumption of breast milk. No difference was seen in the other two dietary patterns. Significant intervention effects were seen on nutrient intake between the GUMLi (intervention) and cows' milk (control) groups, with lower protein and vitamin B12, and higher Fe, vitamin D, vitamin C and Zn intake in the GUMLi (intervention) group. The consumption of GUMLi did not affect dietary patterns, however, GUMLi participants had lower protein intake and higher Fe, vitamins D and C and Zn intake at 2 years of age.

Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis.

BACKGROUND: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. OBJECTIVES: To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. STUDY SELECTION: Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. STUDY APPRAISAL: Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. RESULTS: We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. LIMITATIONS: Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. CONCLUSIONS: Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013953. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Evaluation of the Effect of a Growing up Milk Lite vs. Cow's Milk on Diet Quality and Dietary Intakes in Early Childhood: The Growing up Milk Lite (GUMLi) Randomised Controlled Trial.

scores provide an alternative approach to measuring dietary quality. The Growing Up Milk-Lite (GUMLi) Trial was a multi-centre, double-blinded, randomised controlled trial of children randomised to receive a reduced protein GUM (GUMLi) or unfortified cow's milk (CM). In a secondary analysis of the GUMLi Trial, we used the Probability of Adequate Nutrient Intake (PANDiet) to determine the nutritional adequacy of the diets of participating children living in Auckland. The PANDiet was adapted to the New Zealand Nutrient Reference Values and data from four 24 h Recalls (24HR) collected at months 7, 8, 10, and 11 post-randomisation were used. Differences between randomised groups (GUMLi vs. CM) of the PANDiet and its components were made. Eighty-three Auckland participants were included in the study (GUMLi n = 41 vs. CM n = 42). Total PANDiet scores were significantly higher in the GUMLi group (p < 0.001), indicating better overall nutrient adequacy and diet quality. Dietary intakes of children in both groups met the recommendations for fat, total carbohydrates and most micronutrients; however, protein intakes exceeded recommendations. Consumption of GUMLi was associated with higher nutritional adequacy, with an increased likelihood of meeting nutrient requirements; however, the impact of the family diet and GUMLi on dietary diversity requires further evaluation.

Effects of folic acid food fortification scenarios on the folate intake of a multi-ethnic pregnant population.

OBJECTIVE: To simulate effects of different scenarios of folic acid fortification of food on dietary folate equivalents (DFE) intake in an ethnically diverse sample of pregnant women. DESIGN: A forty-four-item FFQ was used to evaluate dietary intake of the population. DFE intakes were estimated for different scenarios of food fortification with folic acid: (i) voluntary fortification; (ii) increased voluntary fortification; (iii) simulated bread mandatory fortification; and (iv) simulated grains-and-rice mandatory fortification. SETTING: Ethnically and socio-economically diverse cohort of pregnant women in New Zealand.ParticipantsPregnant women (n 5664) whose children were born in 2009-2010. RESULTS: Participants identified their ethnicity as European (56·0 %), Asian (14·2 %), Maori (13·2 %), Pacific (12·8 %) or Others (3·8 %). Bread, breakfast cereals and yeast spread were main food sources of DFE in the two voluntary fortification scenarios. However, for Asian women, green leafy vegetables, bread and breakfast cereals were main contributors of DFE in these scenarios. In descending order, proportions of different ethnic groups in the lowest tertile of DFE intake for the four fortification scenarios were: Asian (39-60 %), Others (41-44 %), European (31-37 %), Pacific (23-26 %) and Maori (23-27 %). In comparisons within each ethnic group across scenarios of food fortification with folic acid, differences were observed only with DFE intake higher in the simulated grains-and-rice mandatory fortification v. other scenarios. CONCLUSIONS: If grain and rice fortification with folic acid was mandatory in New Zealand, DFE intakes would be more evenly distributed among pregnant women of different ethnicities, potentially reducing ethnic group differences in risk of lower folate intakes.

Compared with Cow Milk, a Growing-Up Milk Increases Vitamin D and Iron Status in Healthy Children at 2 Years of Age: The Growing-Up Milk-Lite (GUMLi) Randomized Controlled Trial.

Background: Iron deficiency (ID) and vitamin D deficiency (VDD) are significant pediatric health issues in New Zealand and Australia and remain prevalent micronutrient deficiencies in young children globally. Objective: We aimed to investigate the effect of a micronutrient-fortified, reduced-energy growing-up milk (GUMLi) compared with cow milk (CM) consumed for 1 y on dietary iron and vitamin D intakes and the status of New Zealand and Australian children at 2 y of age. Methods: The GUMLi Trial was a multicenter, double-blind, randomized controlled trial in 160 healthy 1-y-old New Zealand and Australian children conducted in 2015-2017. Participants were randomly assigned 1:1 to receive GUMLi (1.7 mg Fe/100 mL; 1.3 µg cholecalciferol/100 mL) or CM (0.02 mg Fe/100 mL; 0.06 µg cholecalciferol/100 mL) for 12 mo. Secondary outcomes, reported here, included change in dietary iron and vitamin D intakes, iron status, and 25-hydroxyvitamin D [25(OH)D] concentrations from blood samples at age 2 y. All regression models were adjusted for baseline outcome and study center. Results: GUMLi was a large contributor to dietary intakes of iron and vitamin D after 12 mo when compared with intakes from food and CM. The adjusted mean difference between groups for serum ferritin concentrations was 17.8 µg/L (95% CI: 13.6, 22.0 µg/L; P < 0.0001), and for 25(OH)D it was 16.6 nmol/L (95% CI: 9.9, 23.3 nmol/L; P < 0.0001). After 12 mo, ID was present in 16 (24%) participants in the CM group and 5 (7%) participants in the GUMLi group (P = 0.009), and the prevalence of VDD in the CM group increased to 14% (n = 10) and decreased to 3% (n = 2) (P = 0.03) in the GUMLi group. Conclusion: In comparison with CM, GUMLi significantly improved dietary iron and vitamin D intakes and the iron and vitamin D status of healthy children at 2 y of age. This trial was registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12614000918628.

Determinants of folic acid supplement use outside national recommendations for pregnant women: results from the Growing Up in New Zealand cohort study.

OBJECTIVE: To evaluate the sociodemographic and lifestyle factors associated with insufficient and excessive use of folic acid supplements (FAS) among pregnant women. DESIGN: A pregnancy cohort to which multinomial logistic regression models were applied to identify factors associated with duration and dose of FAS use. SETTING: The Growing Up in New Zealand child study, which enrolled pregnant women whose children were born in 2009-2010. SUBJECTS: Pregnant women (n 6822) enrolled into a nationally generalizable cohort. RESULTS: Ninety-two per cent of pregnant women were not taking FAS according to the national recommendation (4 weeks before until 12 weeks after conception), with 69 % taking insufficient FAS and 57 % extending FAS use past 13 weeks' gestation. The factors associated with extended use differed from those associated with insufficient use. Consistent with published literature, the relative risks of insufficient use were increased for younger women, those with less education, of non-European ethnicities, unemployed, who smoked cigarettes, whose pregnancy was unplanned or who had older children, or were living in more deprived households. In contrast, the relative risks of extended use were increased for women of higher socio-economic status or for whom this was their first pregnancy and decreased for women of Pacific v. European ethnicity. CONCLUSIONS: In New Zealand, current use of FAS during pregnancy potentially exposes pregnant women and their unborn children to too little or too much folic acid. Further policy development is necessary to reduce current socio-economic inequities in the use of FAS.

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.

Vitamin D activity of breast milk in women randomly assigned to vitamin D3 supplementation during pregnancy.

BACKGROUND: Human milk is typically low in vitamin D activity (VDA). Whether the vitamin D content of breast milk at birth can be increased by supplementing the mother during pregnancy has not been reported to the best of our knowledge. OBJECTIVE: We examined the effect of vitamin D supplementation during pregnancy on breast-milk VDA in the first 2 mo of lactation. DESIGN: Breast-milk samples were obtained from women who were enrolled in a randomized, double-blinded, placebo-controlled trial of vitamin D supplementation during pregnancy. Pregnant women were enrolled at 27 wk of gestation and randomly assigned to the following 3 groups: a placebo group, a group who received one dosage of daily oral vitamin D3 (1000 IU), or a group who received 2 dosages of daily oral vitamin D3 (2000 IU). Serum 25-hydroxyvitamin D [25(OH)D] was measured at enrollment, at 36 wk of gestation, and in cord blood at birth. Study participants who were breastfeeding were invited to provide breast-milk samples for VDA measurement [concentration of vitamin D2, vitamin D3, 25(OH)D2, and 25(OH)D3] at 2 wk and 2 mo postpartum. A linear mixed model was used to compare breast-milk VDA between the 3 study groups. RESULTS: A total of 75 women provided breast-milk samples (44 women provided breast-milk samples at both 2 wk and 2 mo postpartum). The mean (95% CI) VDA at age 2 wk was 52 IU/L (12, 217 IU/L) in the placebo group, 51 IU/L (17, 151 IU/L) in the 1000-IU group, and 74 IU/L (25, 221 IU/L) in the 2000-IU group; and at age 2 mo, the mean (95% CI) VDA was 45 IU/L (16, 124 IU/L), 43 IU/L (18, 103 IU/L), and 58 IU/L (15, 224 IU/L), respectively. There was no significant interaction in VDA between the sample-collection time and treatment (P = 0.61), but there was a difference between lower- and higher-dosage treatment groups (P = 0.04). CONCLUSION: Maternal vitamin D supplementation during pregnancy of 2000 IU/d (compared with 1000 IU/d and with a placebo) results in a higher VDA of breast milk ≥2 mo postpartum. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12610000483055.

Insufficient vitamin D supplement use during pregnancy and early childhood: a risk factor for positional skull deformation.

Vitamin D insufficiency during pregnancy is associated with disturbed skeletal homeostasis during infancy. Our aim was to investigate the influence of adherence to recommendations for vitamin D supplement intake of 10 µg per day (400 IU) during pregnancy (mother) and in the first months of life (child) on the occurrence of positional skull deformation of the child at the age of 2 to 4 months. In an observational case-control study, two hundred seventy-five 2- to 4-month-old cases with positional skull deformation were compared with 548 matched controls. A questionnaire was used to gather information on background characteristics and vitamin D intake (food, time spent outdoors and supplements). In a multiple variable logistic regression analysis, insufficient vitamin D supplement intake of women during the last trimester of pregnancy [adjusted odds ratio (aOR) 1.86, 95% (CI) 1.27-2.70] and of children during early infancy (aOR 7.15, 95% CI 3.77-13.54) were independently associated with an increased risk of skull deformation during infancy. These associations were evident after adjustment for the associations with skull deformation that were present with younger maternal age and lower maternal education, shorter pregnancy duration, assisted vaginal delivery, male gender and milk formula consumption after birth. Our findings suggest that non-adherence to recommendations for vitamin D supplement use by pregnant women and infants are associated with a higher risk of positional skull deformation in infants at 2 to 4 months of age. Our study provides an early infant life example of the importance of adequate vitamin D intake during pregnancy and infancy.

Global summary of maternal and newborn vitamin D status - a systematic review.

Pregnant women and newborns are at increased risk of vitamin D deficiency. Our objective was to create a global summary of maternal and newborn vitamin D status. We completed a systematic review (1959-2014) and meta-analysis of studies reporting serum 25-hydroxyvitamin D [25(OH)D] concentration in maternal and newborn populations. The 95 identified studies were unevenly distributed by World Health Organization (WHO) region: Americas (24), European (33), Eastern Mediterranean (13), South-East Asian (7), Western Pacific (16) and African (2). Average maternal 25(OH)D concentrations (nmol L(-1) ) by region were 47-65 (Americas), 15-72 (European), 13-60 (Eastern Mediterranean), 20-52 (South-East Asian), 42-72 (Western Pacific) and 92 (African). Average newborn 25(OH)D concentrations (nmol L(-1) ) were 35-77 (Americas), 20-50 (European), 5-50 (Eastern Mediterranean), 20-22 (South-East Asian), 32-67 (Western Pacific) and 27-35 (African). The prevalences of 25(OH)D <50 and <25 nmol L(-1) by WHO region in pregnant women were: Americas (64%, 9%), European (57%, 23%), Eastern Mediterranean (46%, 79%), South-East Asian (87%, not available) and Western Pacific (83%, 13%). Among newborns these values were: Americas (30%, 14%), European (73%, 39%), Eastern Mediterranean (60%, not available), South-East Asian (96%, 45%) and Western Pacific (54%, 14%). By global region, average 25(OH)D concentration varies threefold in pregnant women and newborns, and prevalence of 25(OH)D <25 nmol L(-1) varies eightfold in pregnant women and threefold in newborns. Maternal and newborn 25(OH)D concentrations are highly correlated. Addressing vitamin D deficiency in pregnant women and newborns should be a global priority. To protect children from the adverse effects of vitamin D deficiency requires appropriate interventions during both pregnancy and childhood.

Predictors of vitamin D status in pregnant women in New Zealand.

INTRODUCTION: Newborn vitamin D status is largely determined by maternal vitamin D status during pregnancy. New Zealand has a sun avoidance health policy and minimal dietary vitamin D fortification. Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentration <50 nmol/L) is present in 57% of a sample of newborns from Christchurch and Wellington. To inform vitamin D supplementation policy, our aim was to describe the frequency of, and factors associated with, vitamin D deficiency during pregnancy. METHODS: We enrolled an ethnically diverse sample of pregnant women from a community maternity clinic in South Auckland, New Zealand, with serum 25(OH)D concentration measured at 27 weeks gestation. We examined the associations of enrolment season, maternal demographics, health, sunlight exposure and vitamin D intake with vitamin D deficiency. RESULTS: Vitamin D deficiency was present in 109/259 (42%). Enrolment season (P<0.001) and ethnicity (P=0.003) were independently associated with the odds of vitamin D deficiency, but not sunlight exposure or dietary vitamin D intake. Of those enrolled in winter (June-August)/spring (September-November), vitamin D deficiency was present in 43% of European, 67% of Maori, 80% of Pacific and 59% of women of other ethnic groups. CONCLUSIONS: These findings suggest that New Zealand's targeted strategy for vitamin D supplementation may miss up to 42% of women with vitamin D deficiency in our population. Supplementation for all pregnant women during winter/spring could be an appropriate intervention for prevention of vitamin D deficiency during pregnancy in New Zealand.

Provider engagement and choice in the Lead Maternity Carer System: Evidence from Growing Up in New Zealand.

BACKGROUND: New Zealand (NZ) has a unique choice-based model of maternity care. AIMS: To examine how engagement in antenatal care and choice of Lead Maternity Care provider (LMC) vary with maternal demographics. MATERIALS AND METHODS: Our sample consisted of 6822 women enrolled during 2009 and 2010 into a longitudinal cohort study Growing Up in New Zealand. We asked if women had engaged a LMC, the type of LMC and whether they had a choice of LMC. Associations with maternal ethnicity, age, parity and education and household deprivation were determined. RESULTS: Ninety-eight per cent of women had engaged a LMC provider. Twelve per cent reported not experiencing choice and 11% not receiving their first choice of LMC provider. The reported LMC provider type was independent midwife (66%), hospital midwife (15%), private obstetrician (8%), shared midwife and general practitioner (GP) (5%) and GP-only care (<1%). LMC provider type and choice varied with maternal demographics. Women not engaging a LMC were more likely to be non-European, <20 years or >40 years old, with poorer educational attainment, or living in more deprived households. Women not experiencing choice of provider were more likely to be non-European, <20 years old, or living in more deprived households. CONCLUSIONS: The current unequal distribution of provider engagement and choice in NZ has relevance for a number of specific maternity policies, including policies seeking to improve engagement in antenatal care. The study findings have international relevance as an example of the impact of choice policies on equity.

Early engagement with a Lead Maternity Carer: results from Growing Up in New Zealand.

BACKGROUND: Timely engagement in antenatal care improves maternal and child health outcomes and is an important element of healthcare performance measurement. AIMS: To describe the timeliness of lead maternity carer (LMC) engagement and identify the factors associated with timely engagement. MATERIALS AND METHODS: The Growing Up in New Zealand longitudinal study enrolled a diverse sample of pregnant women during 2009 and 2010. Timely engagement was defined as before ten weeks gestation. Independent associations of LMC type; maternal ethnicity, age, parity and education, and household deprivation with timely engagement were described using odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: Of the 6822 women enrolled, 6661 (98%) stated they had a LMC. Of these 6661, 6012 (90%) reported the time taken to engage a LMC. Eighty-six to 92% of women engaged a LMC in a timely manner depending upon the estimate of gestational time used. Factors independently associated with delayed engagement were Maori (odds ratio (OR) = 0.59, 95% CI 0.44-0.80), Pacific (0.63, 0.46-0.86) or Asian (0.51, 0.39-0.67) ethnicity; first pregnancy (0.71, 0.58-0.88); age <20 years (0.62, 0.41-0.94); socio-economic deprivation (0.69, 0.52-0.92); and LMC type being a hospital midwife (0.47, 0.38-0.60), or a combination of care providers (0.60, 0.42-0.90). CONCLUSIONS: Timeliness of LMC engagement in NZ is poorer for non-European women, younger women, women in their first pregnancy, and women living in more socioeconomically deprived areas. Improving the timeliness of LMC engagement for these groups of women has the potential to reduce inequalities in maternal and child health outcomes.

Reduced primary care respiratory infection visits following pregnancy and infancy vitamin D supplementation: a randomised controlled trial.

AIM: To determine whether vitamin D supplementation reduces primary care visits for acute respiratory infection (ARI). METHODS: A randomised, double-blind, placebo-controlled trial was conducted in New Zealand and powered to determine the vitamin D dose needed to achieve normal vitamin D status during infancy. Healthy pregnant women, from 27 weeks' gestation to birth, and their infants, from birth to age 6 months, were assigned to placebo or one of the two dosages of daily oral vitamin D3 . Woman/infant pairs were randomised to placebo/placebo, 1000 IU/400 IU or 2000 IU/800 IU. For this ad hoc analysis, the primary care records of enrolled children were audited to age 18 months. RESULTS: Two hundred and sixty pregnant women were randomised to placebo (n = 87), lower-dose (n = 87) or higher-dose (n = 86) vitamin D3 . In comparison with the placebo group (99%), the proportion of children making any ARI visits was smaller in the higher-dose (87%, p = 0.004), but not the lower-dose vitamin D3 group (95%, p = 0.17). The median number of ARI visits/child was less in the higher-dose vitamin D3 group from age 6-18 months (placebo 4, lower dose 3, higher dose 2.5; p = 0.048 for higher-dose vitamin D3 vs. placebo). CONCLUSION: Vitamin D3 supplementation during pregnancy and infancy reduces primary care visits for ARI during early childhood.

Vitamin D during pregnancy and infancy and infant serum 25-hydroxyvitamin D concentration.

OBJECTIVE: To determine the vitamin D dose necessary to achieve serum 25-hydroxyvitamin D (25(OH)D) concentration ≥ 20 ng/mL during infancy. METHODS: A randomized, double-blind, placebo-controlled trial in New Zealand. Pregnant mothers, from 27 weeks' gestation to birth, and then their infants, from birth to age 6 months, were randomly assigned to 1 of 3 mother/infant groups: placebo/placebo, vitamin D3 1000/400 IU, or vitamin D3 2000/800 IU. Serum 25(OH)D and calcium concentrations were measured at enrollment, 36 weeks' gestation, in cord blood, and in infants at 2, 4, and 6 months of age. RESULTS: Two-hundred-and-sixty pregnant women were randomized. At enrollment, the proportions with serum 25(OH)D ≥ 20 ng/mL for placebo, lower-dose, and higher-dose groups were 54%, 64%, and 55%, respectively. The proportion with 25(OH)D ≥ 20 ng/mL was larger in both intervention groups at 36 weeks' gestation (50%, 91%, 89%, P < .001). In comparison with placebo, the proportion of infants with 25(OH)D ≥ 20 ng/mL was larger in both intervention groups to age 4 months: cord blood (22%, 72%, 71%, P < .001), 2 months (50%, 82%, 92%, P < .001), and 4 months (66%, 87%, 87%, P = .004), but only in the higher-dose group at age 6 months (74%, 82%, 89%, P = .07; higher dose versus placebo P = .03, lower dose versus placebo P = .21). CONCLUSIONS: Daily vitamin D supplementation during pregnancy and then infancy with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥ 20 ng/mL, with the higher dose sustaining this increase for longer.